A variety of types of sensors have been developed for use in connection with fluidic systems and instruments, such as fluidic-based analysis and biological assay systems and analytical instrument systems. Although it will be appreciated that sensors can be used in a wide variety of different types of fluidic systems and instruments, and in a variety of applications in such systems, for convenience this disclosure will use as an example various types of analytical instrument (“AI”) systems in which sensors may be used, such as liquid and gas chromatography systems, mass spectroscopy systems, and the like. Conventional AI systems also include systems for ion chromatography (IC), high-pressure liquid chromatography, ultra-high pressure liquid chromatography, mass spectrometry systems, micro-flow chromatography systems, nanoflow and nano-scale chromatography systems, capillary electrophoresis systems, reverse-gradient chromatography systems, and systems which include or combine one or more of the foregoing. However, those skilled in the art will appreciate that the discussion of AI systems and instruments is merely for purposes of illustration, and that in addition to AI systems and instruments, sensors may be useful in connection with various types of scientific systems, including for example, hematological systems and instruments, immunoassay instruments and systems, gene sequencing instruments and systems and the like.
In practice, various components in an AI system may be connected by an operator to perform a given task. For example, an operator will select an appropriate mobile phase and column, and then connect a supply of the selected mobile phase and a selected column to a LC system before operation. In order to be suitable for LC applications in this example, each connection must be able to withstand the typical operating pressures of the LC system. If the connection is too weak, it may leak. Because the types of solvents that are sometimes used as the mobile phase are often toxic and because it is often expensive to obtain and/or prepare many samples for use, any such connection failure is a serious concern.
It is fairly common for an operator to connect or disconnect various components in an AI system. Those skilled in the art will appreciate that an “operator” in connection with this disclosure may be an operator of a system or instrument, a maintenance or repair technician, or may be someone who otherwise uses the system or instrument. Given the importance of leak-proof connections in AI systems, the operator must take time to be sure the connection is sufficient each time one is made. Adding, removing, or replacing one or more components in a given AI system may occur several times in a day. Moreover, the time involved in disconnecting and then connecting a given component is unproductive because the AI system is not in use and the operator is engaged in plumbing the system instead of preparing samples or other more productive activities. Hence, the addition, removal or replacement of a component in a conventional AI system can involve a great deal of wasted time and inefficiencies.
In many applications using selector/injector valves to direct fluid flows, and in particular in liquid chromatography, the volume of fluids is small. This is particularly true when liquid chromatography is being used as an analytical method as opposed to a preparative method. Such methods often use capillary columns and are generally referred to as capillary chromatography. In capillary chromatography, it is often desired to minimize the internal volume of the selector or injector valve. One reason for this is that a valve having a large volume will contain a relatively large volume of liquid, and when a sample is injected into the valve the sample will be diluted, decreasing the resolution and sensitivity of the analytical method.
Micro-fluidic analytical processes also involve small sample sizes. As used herein, sample volumes considered to involve micro-fluidic techniques can range from as low as volumes of only several picoliters or so, up to volumes of several milliliters or so, whereas more traditional AI techniques, for example, historically often involved samples of about one microliter to about 100 milliliters in volume. Thus, the micro-fluidic techniques described herein involve volumes one or more orders of magnitude smaller in size than traditional AI techniques. Micro-fluidic techniques can also be expressed as those involving fluid flow rates of about 0.5 mL/minute or less.
As noted, liquid chromatography (as well as other analytical instrument) systems typically include several components. For example, such a system may include a pump; an injection valve or autosampler for injecting the analyte; a precolumn filter to remove particulate matter in the analyte solution that might clog the column; a packed bed to retain irreversibly adsorbed chemical material; the LC column itself; and a detector that analyzes the carrier fluid as it leaves the column. Ion chromatography may also utilize a suppressor column to facilitate detection dynamic range. These various components may typically be connected by a miniature fluid conduit, or tubing, such as metallic or polymeric tubing (for ion chromatography), usually having an internal diameter of 0.003 to 0.040 inch.
All of these various components and lengths of tubing are typically interconnected by threaded fittings. Fittings for connecting various LC system components and lengths of tubing are disclosed in prior patents, for example, U.S. Pat. Nos. 5,525,303; 5,730,943; and 6,095,572, the disclosures of which are all incorporated by reference as if fully set forth herein. Often, a first internally threaded fitting seals to a first component with a ferrule or similar sealing device. The first fitting is threadedly connected through multiple turns by hand or by use of a wrench or wrenches to a second fitting having a corresponding external fitting, which is in turn sealed to a second component by a ferrule or other seal. Disconnecting these fittings for component replacement, maintenance, or reconfiguration often requires the use of a wrench or wrenches to unthread the fittings. Although a wrench or wrenches may be used, other tools such as pliers or other gripping and holding tools are sometimes used. In addition, the use of such approaches to connect components of an LC system often results in deformation or swaging of a ferrule used to provide a leak proof seal of tubing to a fitting or component. This often means that the ferrule and tubing connection, once made, cannot be reused without a risk of introducing dead volumes into the system. In addition, such approaches may involve crushing or deformation of the inner diameter of the tubing, which may adversely affect the flow characteristics and the pressures of the fluid within the tubing.
In such systems, it is often desirable for an operator to monitor or determine various operating parameters, such as pressure of the fluid as it flows in a particular part of the system, flow rate in a particular part of the system, temperature of the fluid in a particular part of the system, and so forth. For example, such detection and monitoring can help avoid blowouts or bursting of fluidic connections or components, such as valves and tubing. In addition, such detection and monitoring is useful in connection with detecting leaks or blockages in the system, which can result in savings with respect to samples and reagents. Since many samples are small and sometimes irreplaceable, such savings can be critical. Moreover, such detection and monitoring can assist in detecting bubbles in the fluid flowpath before they affect or impact the system performance, and in general, such sensors can be used to provide essentially real-time feedback and information regarding system performance, which an operator can then use to make adjustments as desired to enhance and optimize system performance.
Conventional sensors for sensing such parameters and providing information regarding the same have been developed. For example, a liquid flow sensor is commercially available from Sensirion AG of Staefa, Switzerland, and provides a flow sensor with a flow channel in a planar substrate. This sensor allows for biocompatible operations. An example of such a sensor is disclosed in U.S. Pat. No. 7,905,140, issued on Mar. 15, 2011, to Kanne, and titled “Device with Flow Sensor for Handling Fluids.” Such a sensor typically needs some sort of packaging before it can be used in a flowpath or requires assembly and connection with a manifold for use. Such packaging, assembly and connection takes time, skill, and is often difficult and cumbersome. Those skilled in the art will appreciate that other flow sensors and other sensors (e.g., such as for sensing temperature, pressure, or the like) are also commercially available.
While such conventional sensors can be useful, the mounting of such a sensor, and its integration into a system for application, are typically left to the end user. Generally, it tends to be difficult and time-consuming for an end user to integrate such a sensor into a usable package and connect it for use in a fluidics system. Typically, an end user would need to assemble the sensor with several other components to properly install and use the sensor in a fluidics system. In many situations, the sensor, once installed in a system, cannot be reused in another part of the system or in another system. Moreover, once installed and connected, such sensors may be difficult and time-consuming to disconnect. Because such systems are typically expensive, anything that causes or involves downtime of the system while a component such as a sensor is connected or disconnected, can result in substantial costs. In addition, such sensors typically do not provide much variation as to their size, shape, and fluid path, which means that mounting the sensor on any holding device, or connecting the sensor in a system with other components, may be difficult and time-consuming because the size, shape, and/or fluid path of the sensor that is commercially available may not match the portion of the system for which the sensor is intended to be used.
Many conventional sensors typically are used in only a single-ended application, such as the placement of a sensor adjacent or near a branch of the fluid flow system which is not swept by the main flow of the fluid. For example, this occurs when the sensor is placed adjacent or near a fluid flow path that is essentially a branch off of the main or primary fluid flow path. One potential problem with such sensors is that they often involve carryover issues, such as the addition of potential deadspace or dead volume into the flow path of a system, and as noted often are not swept by the main flow of the fluid. Such dead volume is problematic for a number of reasons, including the potential to contaminate samples as well as affect the outcome or results of successive tests on different samples. Moreover, the dead volume allows the possibility that the system can trap gas bubbles in a pocket within the system, and such bubbles may cause a variety of problems, such as by increasing the noise in the results and measurements obtained from the system and by making it difficult to ensure that the system results are precise and accurate.
A number of conventional approaches have been tried with respect to providing pressure sensors for use in various applications. For example, U.S. Pat. No. 5,852,244, issued on Dec. 22, 1998 and titled “Non-Fluid Conducting Pressure Sensor Module Having Non-Contaminating Body and Isolation Member,” describes a pressure sensor configuration which may be positioned in-line with a fluid path containing corrosive materials, such as those used to manufacture semiconductors. Similarly, U.S. Pat. No. 5,869,766, issued on Feb. 9, 1999, and titled “Non-Contaminating Pressure Transducer Module,” describes the use of an isolation member to isolate the pressure sensor from exposure to ultra high purity fluids.
Another example of a proposed inline pressure sensor can be found in U.S. Pat. No. 6,948,373, issued on Sep. 27, 2005, and titled “Inline Pressure Sensor.” In this particular patent, a pressure sensing section and a sensor element are provided in a housing which has two ports and forms a flow path that can be considered convex, with the goal of minimizing dead volume.
Another approach can be found in U.S. Pat. No. 3,880,151, issued on Apr. 29, 1975, and titled “Pressure Receiver.” In this patent, a pressure receiver for determining intravascular pressure is described, which includes a chamber having a truncated or frusto-conical cone and having a conical member extending in an opposite and symmetrical direction. In U.S. Pat. No. 4,920,272, issued on May 1, 1990, and titled “Gel-Filled Blood Pressure Transducer,” another pressure transducer for measuring blood pressure is provided. In this latter patent, the pressure transducer includes a body having a recess with an opening covered by a flexible diaphragm, with the sensor placed over a hole opposite the diaphragm. The sensor includes a dielectric gel in the recess to transmit to the sensor the variations in pressure imparted to the diaphragm.
Applicants hereby incorporate by reference as if fully set forth herein the previously discussed U.S. Pat. Nos. 3,880,151, 4,920,972, 5,852,244, 5,899,766, and 6,948,373.
Those skilled in the art will appreciate that the modular sensor system disclosed below overcomes a number of disadvantages of conventional sensors and housings for same, and will appreciate that advantages of the modular sensor as disclosed below.